Selected Topics on Mathematical Models in Immunology and Medicine

In 1988 the new IIASA project on System Immunology was inaugurated. The new activity focuses theoretical and experimental research in immunology and system mathematics to experimental planning and prediction for relevant disease applications and systematic understanding of immunology. IIASA analysis and simulation should lead to an effective plan of successive experiments to identify and to quantify particularly sensitive parameters in this most complex system of information processing, decision and control. The integration of such diverse disciplines is extremely difficult but some basis has already been established. For several years IIASA has sponsored international workshops dealing with dynamical systems and their applications to biology. These include: (1) The conference on "Dynamics of Macrosystems"; (2) The Working Conference on "Theoretical Immunology"; (3) The Workshop on "Selected Topics in Biomathematics"; The present volume contains the proceedings of the latest Workshop "Mathematical Modelling in Immunology and Medicine", Part 1 deals with the mathematical models of autoimmune, infectious diseases and AIDS. The models are studied with the intent to establish a basis for more effective treatment. In Part 2, questions of computer simulation and data analysis in cancer research are analyzed. Part 3 is devoted to the models for antibody binding, immunoassay dynamics and immunogenetic systems. The problems of system analysis and medical decision making are discussed in Part 4

The isolation and characterisation of immune complexes in human body fluids

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Association of FCGR3A and FCGR3B haplotypes with rheumatoid arthritis and primary Sjögren's syndrome [POSTER PRESENTATION]

Background Rheumatoid arthritis (RA) is an autoimmune disease that is thought to arise from a complex interaction between multiple genetic factors and environmental triggers. We have previously demonstrated an association between a Fc gamma receptor (FcγR) haplotype and RA in a cross-sectional cohort of RA patients. We have sought to confirm this association in an inception cohort of RA patients and matched controls. We also extended our study to investigate a second autoanti-body associated rheumatic disease, primary Sjögren's syndrome (PSS). Methods The FCGR3A-158F/V and FCGR3B-NA1/NA2 functional polymorphisms were examined for association in an inception cohort of RA patients (n = 448), and a well-characterised PSS cohort (n = 83) from the United Kingdom. Pairwise disequilibrium coefficients (D') were calculated in 267 Blood Service healthy controls. The EHPlus program was used to estimate haplotype frequencies for patients and controls and to determine whether significant linkage disequilibrium was present. A likelihood ratio test is performed to test for differences between the haplotype frequencies in cases and controls. A permutation procedure implemented in this program enabled 1000 permutations to be performed on all haplotype associations to assess significance. Results There was significant linkage disequilibrium between FCGR3A and FCGR3B (D' = -0.445, P = 0.001). There was no significant difference in the FCGR3A or FCGR3B allele or genotype frequencies in the RA or PSS patients compared with controls. However, there was a significant difference in the FCGR3A-FCGR3B haplotype distributions with increased homozygosity for the FCGR3A-FCGR3B 158V-NA2 haplotype in both our inception RA cohort (odds ratio = 2.15, 95% confidence interval = 1.1–4.2 P = 0.027) and PSS (odds ratio = 2.83, 95% confidence interval = 1.0–8.2, P = 0.047) compared with controls. The reference group for these analyses comprised individuals who did not possess a copy of the FCGR3A-FCGR3B 158V-NA2 haplotype. Conclusions We have confirmed our original findings of association between the FCGR3A-FCGR3B 158V-NA2 haplotype and RA in a new inception cohort of RA patients. This suggests that there may be an RA-susceptibility gene at this locus. The significant increased frequency of an identical haplotype in PSS suggests the FcγR genetic locus may contribute to the pathogenesis of diverse autoantibody-mediated rheumatic diseases

Construction and characterisation of attenuated derivatives of Pasteurella multocida: serotype B:2 strains

The project was concerned with the construction of defined attenuated derivatives of P. multocida serotype B:2 strains, causative agents of haemorrhagic septicaemia, and attempts were made to construct defined mutations in genes such as aroA, cya, and galE loci that have been used to induce attenuation in other bacterial strains. Mutants defective in the aroA gene were constructed by allelic exchange of the locus in the chromosome of the wild-type strains with a cloned aroA gene interrupted with a cassette encoding kanamycin resistance (KmR). The aroA defective strains were confirmed by PCR, Southern blotting, lack of growth on minimal medium and by enzyme assay. KmR inactivated aroA mutants JRMT1 and JRMT2 strains derived from P. multocida 85020 and Quetta strains, respectively, were highly attenuated in a mouse model, with an LD50 108 C.F.U./mouse after injection intraperitoneally (i.p.). In contrast, the wild-type strains had LD50 <50 C.F.U./mouse by this route. Vaccination once by the i.p. route or twice by the i.n. route with these aroA mutants gave complete protection to the mice against subsequent challenge i.p. with 10,000 LD50 of the homologous wild-type strain or 1000 LD50 of the heterologous wild-type strain. Vaccination with these by the s.c. route was not protective. When high doses of the attenuated strains were inoculated by the i.p. or i.n. routes, there was some spread to the internal organs but the organisms were cleared by 24 and 72 hrs respectively. In contrast, the wild-type parent strains spread rapidly and multiplied in high numbers and killed the mice by 24 and 96 hrs respectively

BIOLOGICAL INSPIRED INTRUSION PREVENTION AND SELF-HEALING SYSTEM FOR CRITICAL SERVICES NETWORK

With the explosive development of the critical services network systems and Internet, the need for networks security systems have become even critical with the enlargement of information technology in everyday life. Intrusion Prevention System (IPS) provides an in-line mechanism focus on identifying and blocking malicious network activity in real time. This thesis presents new intrusion prevention and self-healing system (SH) for critical services network security. The design features of the proposed system are inspired by the human immune system, integrated with pattern recognition nonlinear classification algorithm and machine learning. Firstly, the current intrusions preventions systems, biological innate and adaptive immune systems, autonomic computing and self-healing mechanisms are studied and analyzed. The importance of intrusion prevention system recommends that artificial immune systems (AIS) should incorporate abstraction models from innate, adaptive immune system, pattern recognition, machine learning and self-healing mechanisms to present autonomous IPS system with fast and high accurate detection and prevention performance and survivability for critical services network system. Secondly, specification language, system design, mathematical and computational models for IPS and SH system are established, which are based upon nonlinear classification, prevention predictability trust, analysis, self-adaptation and self-healing algorithms. Finally, the validation of the system carried out by simulation tests, measuring, benchmarking and comparative studies. New benchmarking metrics for detection capabilities, prevention predictability trust and self-healing reliability are introduced as contributions for the IPS and SH system measuring and validation. Using the software system, design theories, AIS features, new nonlinear classification algorithm, and self-healing system show how the use of presented systems can ensure safety for critical services networks and heal the damage caused by intrusion. This autonomous system improves the performance of the current intrusion prevention system and carries on system continuity by using self-healing mechanism

Major histocompatibility complex class II expression on ovine T cells

The expression of major histocompatibility complex (MHC) class II gene products is tightly regulated and is normally confined to professional antigen presenting cells (B cells, dendritic cells, monocytes). However many cells can be induced to express MHC class II molecules, for example human T cells do not express class II but synthesize and express high levels upon activation. In sheep, a percentage of resting T cells express class II and upon activation there is increased expression of the different MHC class II molecules (Dutia et at, 1993a). The significance of the increased class II expression after activation of T cells is unclear.In this study the expression of MHC class II molecules on T cells from various immunological compartments of the sheep was examined. Monoclonal antibodies (mAbs) were characterized which react specifically with the homologues of human DRa andDQa molecules. The expression of these antigens was established on B cells and T cell subsets derived from peripheral blood, efferent lymph and afferent lymph. B cells from each of the lymphocyte sources expressed both DRa andDQa antigens. Variable expression on T cells was found. Each of the T cell subsets expressed both DR and DQ molecules at much higher levels in afferent lymph. DR expression on peripheral blood lymphocytes and efferent lymphocytes was higher than DQ on each of the T cell subsets. Afferent lymphocytes represent memory type cells and class II DR expression on these T cells may mark activation status.Expression of the class II subtypes was also examined on in vivo activated T cells and correlated with expression of activation markers. Increased expression of class II molecules was coincident with the increased expression of activation markers in each of the T cell subsets with the exception of y5 cells. The lack of correlation on y5 T cells may be a reflection on the type of antigen used. Levels of DQ expression on CD4 positive cells after activation showed a more dramatic increase than levels of DR expression.R expression. Cytokine profiles of concanavalin A (Con A) activated-T cells (DR positive) were examined and compared with that of DR negative T cells. The data reveal that IL-6 mRNA production correlated with DR expression. IL-6 was induced after activation of the total T cell population and was not induced in the DR negative T cells. No detectable differences in IL-4, IL-10 and ylFN mRNA profiles were observed between the total T cell population and the DR negative T cells.The increased expression of class II molecules after in vivo activation coincided with the increased expression of activation markers. Correlation with activation markers did not provide further insight into the possibility that DR and DQ molecules may fulfil different functional roles whereas examination of cytokines secreted revealed that DR expression correlated with IL-6 production after Con A activation. This is indicative of a functionally distinct immunoregulatary role for DR positive T cells. The differential expression of class II molecules may fulfil distinct functions in regulating the outcome of T cell activation and the resultant effector function.Using the MACS cell separation technique, a novel lymphocyte population was identified in sheep. These lymphocytes were CD3 positive suggesting they are of the T cell lineage, however they did not express markers for CD4, CD8 or y§ T cells. This null cell population represent approximately 5% of the efferent lymphocytes

The Ro/SSA Complex in Systemic Lupus Erythematosus Patients

In this work the involved mechanisms between Ro/SSA complex, composed also by the tripartite motif 21 (TRIM21alpha) and trove domain 2 (TROVE2) proteins, with respect to systemic lupus erythematosus (SLE) autoantibodies is studied. The work is divided in three chapters: I- In vitro and in silico analysis of the molecular recognition between lupus autoantibodies and TRIM21alpha Fc Receptor ; II- In vitro evidence of bipolar-bridged immune TROVE2 complexes in the pathogenesis of systemic lupus erythematosus and III- Label-free piezoelectric biosensor for prognosis and diagnosis of Systemic Lupus Erythematosus. Samples of lupic patients and health subjects were kindly provided by La Fe hospital, accordingly the required protocols. After its extraction and purification, the immunoglobulin samples were obtained to study in vitro protein interactions and the involved mechanism by using a quartz crystal microbalance with dissipation factor attributions, and dual polarization interferometry. Techniques such, polarization modulation infrared interferometry, x-ray photoelectron interferometry and contact angle measurement were used in order to characterize surfaces. Pre-steady-state analysis revealed an antibody bipolar bridging involved in both TRIM21alpha and TROVE2 proteins. Identification of the main immunodominant human linear epitope for TRIM21alpha was finely mapped using a series of overlapping synthetic polypeptides with a size of 21 amino acids. The epitopes recognised by autoantibodies for this protein spanned the linear sequence from the aminoacid 151 to 183, and a conformational epitope for SLE patients and healthy subjects, respectively. Autoantibodies from lupic patients targeted protein epitopes, allowing health subjects to be discriminated. Major Histocompatibility Complex Class-II binding peptide prediction results corroborated the sequence as the immunodominant linear epitope, mostly coded as the HLA DRB1*1304 allele for SLE patients, and HLA DRB1*0806 for controls. The subdominant epitope corresponded to the PRY-SPRY domain, recently known as mammalian Fc receptor. Finally, the TRIM21alpha protein structure was modeled by a new homology modeling, never before presented. From the TROVE2 protein, the major linear epitope recognized by autoantibodies correspond to the sequence from the aminoacid 160 to 210 for healthy subjects. However, the major epitope in SLE serum is undiscovered. We suggest that the difference between epitopes could correspond to a majority necrosis-induced specificity in SLE patients, and an apoptotic via in healthy subjects. TROVE2 showed the ability to bind to Fcs, depending on alkaline earth cations in solution. The results suggest that the TROVE2-TRIM21alpha binding is a calcium-dependent protein interaction linked through the MIDAS-like motif in the vWFA-like domain. Finally, a pratical consequence of all study was the development of label-free biosensing method, based in microbalance technology, for in vitro diagnostics of systemic lupus erythematosus patients, allowing the premature sensing of autoantibodies against TRIM21alpha and TROVE2 protein, in advance of the clinical illness symptoms appear.En este trabajo se ha estudiado el mecanismo involucrado entre el complejo Ro/SSA, compuesto también por las proteínas tripartite motif 21 alpha(TRIM21alpha;) y trove domain 2 (TROVE2) con respecto a autoanticuerpos de pacientes que tienen lupus eritematoso sistémico, en comparación con autoanticuerpos de personas sanas. El estudio comprende tres capítulos: I- Análisis in vitro e in silico del reconocimiento molecular entre autoanticuerpos de lupus y receptor TRIM21alpha; Fc; II- Evidencias in vitro de complejos inmunes TROVE2 bipolares con puentes en la patogénesis del lupus eritematoso sistémico y III- Biosensor piezoeléctrico libre de marcaje para el pronóstico y el diagnóstico del lupus eritematoso sistémico. Las muestras de pacientes lúpicos y personas sanas fueron proporcionadas por el hospital La Fe de acuerdo con los protocolos establecidos. Tras una etapa de extracción y purificación de las inmunoglobulinas fueron estudiadas la interacción de proteínas in vitro utilizando una microbalanza de cristal de cuarzo con atribución de factor de disipación e interferometria de polarización dual. Técnicas de caracterización como espectroscopía infrarroja de reflexión-absorción por modulación de la polarización, espectroscopía fotoelectrónica de rayos-x y análisis de ángulo de contacto fueron utilizadas con la finalidad de caracterizar superficies. El análisis del estado pre estacionario ha revelado un mecanismo de puente bipolar para las dos proteínas, TRIM21alpha; y TROVE2. Tras su identificación, el epítopo linear inmunodominante fue mapeado para TRIM21alpha;, utilizando una serie de polipéptidos sintéticos superpuestos de 21 aminoácidos. Los epitopos reconocidos por autoanticuerpos para esta proteína abarca la secuencia lineal a partir del aminoácido 151 hasta el 183 para epitopos de pacientes lúpicos y sujetos sanos, respectivamente. Autoanticuerpos de pacientes lúpicos reconocieron epítopos de proteínas, permitiendo la discriminación de pacientes sanos. Los resultados de la unión del Complejo Mayor de Histocompatibilidad clase II con el péptido de unión corroboraron la secuencia cómo el epítopo lineal inmunodominante, codificado como el alelo HLA DRB1 * 1304 para pacientes con LES y HLA DRB1 * 0806 para los controles. El epitopo subdominante corresponde al dominio PRY-SPRY, recientemente conocido receptor Fc de mamífero. Finalmente, la estructura de la proteína TRIM21alpha; fue determinada utilizando un nuevo modelo de homología no presentado antes. De la proteína TROVE2, el epitopo lineal immunodominante reconocido por los autoanticuerpos corresponde a la secuencia que pudiera corresponder del aminoácido 160 hasta 210 para sujetos sanos. Sin embargo, el epitopo mayoritario en sueros lúpicos no fue determinado. Se sugiere que la diferencia entre los epitopos se corresponde mayoritariamente a una necrosis-inducida en pacientes lúpicos, y a una vía apoptótica en pacientes sanos. TROVE2 presentó la habilidad de unirse a Fcs dependiendo de los cationes alcalinos presentes en la disolución. Los resultados sugieren que la unión TROVE2-TRIM21alpha; es dependiente de la interacción con calcio vinculada a través del motivo MIDAS en el dominio vWFA. Finalmente, una consecuencia práctica de todo el estudio fue el desarrollo de un biosensor libre de marcaje para diagnóstico in vitro de lupus eritematoso sistémico, permitiendo la detección prematura de autoanticuerpos anti TRIM21alpha; y anti TROVE2, varios años antes de la aparición de los síntomas clínicos de la enfermedad.En aquest treball s'ha estudiat el mecanisme involucrat en el complex Ro/SSA, compost per les proteïnes tripartite motif 21 (TRIM21alpha;) i trove domain 2 (TROVE2) respecte a autoanticossos de pacients que tenen lupus eritematós sistèmic, en comparació amb autoanticossos de persones sanes. L'estudi es divideix en tres capítols: : I- Anàlisi in vitro i in silico del reconeixement molecular entre autoanticossos de lupus i receptor TRIM21alpha; Fc; II- Evidències in vitro de complexos immunes TROVE2 bipolars amb ponts en la patogènesi del lupus eritematós sistèmic i III-Biosensor piezoelèctric lliure de marcatge per al pronòstic i el diagnòstic del lupus eritematós sistèmic. Les mostres de pacients lúpics y persones sanes van ser amablement proporcionades per l'hospital La Fe d'acord amb els protocols establerts. Després d'una etapa de purificació adequada, el pool de mostres de immunoglobulines va ser estudiat les interaccions in vitro de les proteïnes utilitzant una microbalança de cristall de quars amb atribució de factor de dissipació i interferometria de polarització dual. Tècniques de caracterització, como ara espectroscòpia de infraroja de reflexió-absorció per modulació de la polarització, espectroscòpia fotoelèctrica de rajos X i anàlisi d'angle de contacte van ser emprades amb per tal de caracteritzar les superfícies. L¿anàlisi de l`estat preestacionari ha revelat un mecanisme de pont bipolar que involucra les dos proteïnes, TRIM21alpha; i TROVE2. Una vegada identificat, va ser mapat l'epítop immunodominant lineal per a TRIM21alpha; emprant una sèrie de polipèptids sintètics superposats de 21 aminoàcids. Els epítops reconeguts per autoanticossos per a aquesta proteïna engloben la seqüència lineal a partir de l'aminoàcid 151 fins al 183 per a epítops de pacients lúpics y subjectes sans, respectivament. Autoanticossos de pacients lúpicos van reconèixer epítops de proteïnes, fet que va permetre la discriminació de pacients sans. Els resultats de la unió del Complexe Major de Histocompatibilitat classe II amb el pèptid de unió van corroborar la seqüència com l'epítop lineal immunodominant, codificat com l'al·lel HLA DRB1 * 1304 per a pacients amb LES i HLA DRB1 * 0806 per als controls. L'epítop subdominant correspon al domini PRY-SPRY, recentment conegut receptor Fc de mamífer. Finalment, l'estructura de la proteïna TRIM21alpha; va ser determinada utilitzant un nou model d'homologia no presentat abans. De la proteïna TROVE2, l'epítop lineal immunodominant reconegut pels autoanticossos correspon a la seqüència que pogués correspondre l'aminoàcid 160 fins al 210 per a subjectes sans. No obstant això, l'epítop majoritari en sèrums lúpics no va ser determinat. Es suggereix que la diferència entre els epítops es correspon majoritàriament a una necrosis induïda en pacients lúpics i a una via apoptòtica en pacients sans. TROVE2 va mostrar l'habilitat de unir-se a Fcs en funció dels cations alcalins presents en la dissolució. Els resultats suggereixen que la unió TROVE2-TRIM21alpha; depèn de la interacció amb calci vinculada a través del motiu MIDAS en el domini vWFA. Finalment, la conseqüència pràctica de tot l'estudi va ser el desenvolupament d'un biosensor sense marcatge per al diagnòstic in vitro de lupus eritematós sistèmic, el qual permet la detecció prematura d'autoanticossos cap a les proteïnes TRIM21alpha; i TROVE2 anys abans de l'aparició dels símptomes clínics de la malaltia.Do Nascimento, NM. (2017). The Ro/SSA Complex in Systemic Lupus Erythematosus Patients [Tesis doctoral no publicada]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/80534TESI

Comparative study of the opportunistic yeasts Candida glabrata and Candida bracarensis infection strategies

Dissertação de mestrado em Genética MolecularYeasts of the genus Candida are important human pathogens. A new species, Candida bracarensis, was recently described revealing phenotypic and genetic similarities with Candida glabrata, a widespread pathogen, and also with Saccharomyces cerevisiae. The incidence of C. bracarensis has increased globally being now regarded as an emergent fungal pathogen. However, little is known about its characteristics as a pathogenic agent and the interaction with its host. The aim of this work was to compare C. bracarensis with C. glabrata and S. cerevisiae concerning their virulence atributes and the interaction with the host. The analysis of virulence factors has an important role in the study of pathogens and their strategies of infection. However, most of the virulence attributes of the successful pathogen C. albicans are absent in C. glabrata. Here, the inability of C. glabrata to produce secreted aspartyl proteinases (Sap) or hyphae was confirmed. Moreover, we show in this study that all C. bracarensis strains analysed failed to produce Sap and to filament. Phagocytosis plays a critical role in innate immunity, facilitating the removal and killing of pathogens, and priming the adaptive immune response. The phagocytosis rate of the different yeast species was evaluated in murine and human macrophages. C. glabrata was phagocytosed at higher rates than the other two yeast species, being S. cerevisiae the one inducing the lowest phagocytosis rate. Upon interaction with pathogens, phagocytes rapidly produce ROS to destroy invading microbes, however, several pathogens have developed strategies to evade this microcidal mechanism. Here, it is shown that not only viable C. glabrata and C. bracarensis could suppress ROS production, but unexpectedly, S. cerevisiae could reduce ROS production to more than a half. Although these results do not by themselves fully elucidate the disparate incidence of C. glabrata vs C. bracarensis, they nevertheless contribute to better understand the differences on the interaction of these two related species with the host.As leveduras do género Candida são importantes agentes patogénicos em infeções fúngicas humanas. Recentemente foi descrita uma nova espécie, Candida bracarensis, que se assemelha tanto fenotípica como genotipicamente com Candida glabrata e também com Saccharomyces cerevisiae. A incidência desta nova espécie tem vindo a aumentar, estando entre os fungos considerados emergentes. Contudo, muito pouco se conhece acerca das suas características como patogéneo, dos seus fatores de virulência e sobre a sua interação com o hospedeiro. Assim, o objetivo deste projeto foi comparar C. bracarensis, C. glabrata e S. cerevisiae no que diz respeito aos mecanismos de interação com o hospedeiro. A análise dos fatores de virulência tem um papel importante no estudo de agentes patogênicos e das suas estratégias de infecção. No entanto, a maioria dos factores de virulência do agente oportunista bem sucedido C. albicans estão ausentes em C. glabrata. Neste estudo, confirmou-se a incapacidade de C. glabrata de produzir proteinases asparticas (Sap) ou hifas. Além disso, mostramos neste estudo que todas as estirpes de C. bracarensis analisadas não conseguiram produzir Sap nem filamentar. A fagocitose desempenha um papel crítico na imunidade inata, facilitando a remoção e morte de agentes patogênicos e estimulando a resposta imune adaptativa. A taxa de fagocitose das diferentes espécies de levedura foi avaliada em macrófagos murinos e macrófagos humanos. C. glabrata foi fagocitada a taxas superiores do que as outras duas espécies de leveduras, sendo S. cerevisiae o que induz a menor taxa de fagocitose. Após a interação com agentes patogênicos, os fagócitos produzem rapidamente ROS para destruir microrganismos invasores, no entanto, vários microrganismos desenvolveram estratégias para evitar esse mecanismo microbicida. Aqui, mostra-se que não só C. glabrata e C. bracarensis apresentam capacidade de suprimir a produção de ROS, mas, inesperadamente, S. cerevisiae consegue reduzir a produção de ROS para mais de metade. Ainda que estes resultados não expliquem por si só a disparidade encontrada na incidência de C. glabrata e C. bracarensis, contribuem no entanto para um melhor conhecimento da interação destas duas espécies com o hospedeiro

Nuevas estrategias para el desarrollo de biosensores ópticos aplicados al análisis de micotoxinas y hongos toxigénicos en alimentos

Tesis inédita de la Universidad Complutense de Madrid, Facultad de Ciencias Químicas, Departamento de Química Analítica, leída el 15-07-2019Mycotoxins are a diverse group of low molecular weight compounds produced as secondary metabolites by numerous species of filamentous fungi. This assemblage is chemically and toxigenically rather heterogeneous, but generally these toxins are known to cause disease and death in human and other vertebrates even at low concentrations. Mycotoxigenic fungi grow on a wide range of conditions and they can produce mycotoxins into the matrices on which they grow, often food intended for human consumption or animal feed. As a result of the ubiquitous nature of mycotoxigenic fungi, particularly in temperate and tropical regions of the world, mycotoxin contamination is often inevitable, and some calculations have estimated that approximately 25–50% of world crops are contaminated with these toxins. Although the awareness related to the hazards of mycotoxins as food and feed contaminants is growing, there are no absolute measures available for eliminating mycotoxins from agricultural products. While mycotoxin occurrence in the field can be decreased by good agronomic practices and planting resistant varieties, in the end, analytical methods capable of detecting mycotoxins and toxigenic fungi even at low concentration are of key importance for ensuring food safety...Las micotoxinas son metabolitos secundarios tóxicos producidos por algunas cepas de hongos que contaminan alimentos, especialmente cereales y hortalizas. Estos compuestos de bajo peso molecular son químicamente y toxigénicamente heterogéneos; sin embargo, muchas de estas toxinas pueden originar enfermedades, y en ocasiones la muerte, tanto en humanos como en otros vertebrados. Los hongos toxigénicos crecen en muchas condiciones muy diversas, lo que puede dar lugar a la aparición de micotoxinas en los alimentos destinados tanto al consumo humano como al animal. Los hongos toxigénicos están ampliamente distribuidos por todo el mundo, particularmente en las regiones templadas y tropicales, por lo que la contaminación natural por micotoxinas es casi inevitable. De hecho, se estima que aproximadamente el 25–50% de los cultivos mundiales están contaminados por estas toxinas, y la preocupación sobre los peligros asociados a su presencia en alimentos es cada día mayor. Actualmente, no existen alternativas viables para su eliminación en los productos agrícolas; aunque el empleo de buenas prácticas agrícolas o la plantación de variedades resistentes a los hongos, pueden ayudar a mejorar este problema. En cualquier caso, se requieren métodos analíticos sensibles y selectivos para la detección de micotoxinas y hongos toxigénicos, a bajas concentraciones, afin de garantizar la seguridad alimentaria...Depto. de Química AnalíticaFac. de Ciencias QuímicasTRUEunpu